Nuclear Factor κB inducing kinase activation as a mechanism of pancreatic beta cell failure in obesity

ABSTRACT: The NF-κB pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic beta cell dysfunction in the metabolic syndrome. While canonical NF-κB signaling is well studied, there is little information on the divergent non-canonical NF-κB pathway in the context of pancreatic islet dysfunction in diabetes. Here, we demonstrate that pharmacological activation of the non-canonical NF-κB inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. Further, we identify NIK as a critical negative regulator of beta cell function as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which e

ORGANISM(S): Mus musculus

SUBMITTER: Jianmin Wu 

PROVIDER: E-GEOD-68317 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress